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Boevee S.J.,Erasmus Medical Center | Venderbos L.D.F.,Erasmus Medical Center | Tammela T.L.J.,University of Tampere | Nelen V.,Provincial Institute for Hygiene | And 6 more authors.
European Journal of Cancer | Year: 2010

Objective: To evaluate a change in tumour characteristics and applied treatments over time in the control arm of all centres of the European Randomized study of Screening for Prostate Cancer (ERSPC) and to compare this with similar data of the screening arm. Methods: Between 1993 and 2003, 182,160 men, aged 50-74 years, were randomised to the screening arm (N = 82,816) and the control arm (N = 99,184). Men in the screening arm were offered Prostate Specific Antigen (PSA) testing every 4 years whilst men in the control arm received usual care. Tumour characteristics and treatment were evaluated in all men diagnosed with prostate cancer up to December 2006 or the third screening round. Data on the control arm were divided into 3 periods: 1994-1998, 1999-2002 and 2003-2006. Results: Tumour characteristics were more favourable over time in both the control and the screening arm, with especially increasing proportions of T1C tumours with 29% in 1994-1998 versus 50% in 2003-2006 and 48% at the initial screening round versus 75% at the third screening round, respectively. Tumour characteristics observed in the last period of the control arm were comparable to tumour characteristics in the initial screening round. In the control arm, treatment changed over time with surgery as the most common treatment in the entire observed period, but almost doubling of expectant management and the combination of hormone therapy and radiotherapy over time. In the initial screening round, surgery was the most common treatment (42%), changing over time to expectant management as the most frequently applied treatment in the third screening round (33%). Conclusion: Tumour characteristics in the control arm became more favourable over time and show similarity with prostate cancer cases detected at the initial screening round. The most prominent change in treatment over time was an increase of application of expectant management in both arms of the ERSPC. These observations reflect an increasing rate of opportunistic testing over time in men randomised to the control arm. © 2010 Elsevier Ltd. All rights reserved.

PubMed | Service de Genetique Medicale Maternite, Provincial Institute for Hygiene, CIBER ISCIII, University of Southampton and 16 more.
Type: Journal Article | Journal: Birth defects research. Part A, Clinical and molecular teratology | Year: 2016

Surveillance of congenital anomalies is important to identify potential teratogens. Despite known associations between different anomalies, current surveillance methods examine trends within each subgroup separately. We aimed to evaluate whether hierarchical statistical methods that combine information from several subgroups simultaneously would enhance current surveillance methods using data collected by EUROCAT, a European network of population-based congenital anomaly registries.Ten-year trends (2003 to 2012) in 18 EUROCAT registries over 11 countries were analyzed for the following groups of anomalies: neural tube defects, congenital heart defects, digestive system, and chromosomal anomalies. Hierarchical Poisson regression models that combined related subgroups together according to EUROCATs hierarchy of subgroup coding were applied. Results from hierarchical models were compared with those from Poisson models that consider each congenital anomaly separately.Hierarchical models gave similar results as those obtained when considering each anomaly subgroup in a separate analysis. Hierarchical models that included only around three subgroups showed poor convergence and were generally found to be over-parameterized. Larger sets of anomaly subgroups were found to be too heterogeneous to group together in this way.There were no substantial differences between independent analyses of each subgroup and hierarchical models when using the EUROCAT anomaly subgroups. Considering each anomaly separately, therefore, remains an appropriate method for the detection of potential changes in prevalence by surveillance systems. Hierarchical models do, however, remain an interesting alternative method of analysis when considering the risks of specific exposures in relation to the prevalence of congenital anomalies, which could be investigated in other studies. Birth Defects Research (Part A) 106:480-10, 2016. 2016 Wiley Periodicals, Inc.

PubMed | Medical University of Graz, Health Service Executive, Net Ukraine and Khmelnytsky Perinatal Center, Provincial Institute for Hygiene and 18 more.
Type: Journal Article | Journal: American journal of medical genetics. Part A | Year: 2016

The aim of this study was to examine the prevalence of trisomies 18 and 13 in Europe and the prevalence of associated anomalies. Twenty-five population-based registries in 16 European countries provided data from 2000-2011. Cases included live births, fetal deaths (20+ weeks gestation), and terminations of pregnancy for fetal anomaly (TOPFAs). The prevalence of associated anomalies was reported in live births. The prevalence of trisomy 18 and trisomy 13 were 4.8 (95%CI: 4.7-5.0) and 1.9 (95%CI: 1.8-2.0) per 10,000 total births. Seventy three percent of cases with trisomy 18 or trisomy 13 resulted in a TOPFA. Amongst 468 live born babies with trisomy 18, 80% (76-83%) had a cardiac anomaly, 21% (17-25%) had a nervous system anomaly, 8% (6-11%) had esophageal atresia and 10% (8-13%) had an orofacial cleft. Amongst 240 Live born babies with trisomy 13, 57% (51-64%) had a cardiac anomaly, 39% (33-46%) had a nervous system anomaly, 30% (24-36%) had an eye anomaly, 44% (37-50%) had polydactyly and 45% (39-52%) had an orofacial cleft. For babies with trisomy 18 boys were less likely to have a cardiac anomaly compared with girls (OR=0.48 (0.30-0.77) and with trisomy 13 were less likely to have a nervous system anomaly [OR=0.46 (0.27-0.77)]. Babies with trisomy 18 or trisomy 13 do have a high proportion of associated anomalies with the distribution of anomalies being different in boys and girls.

PubMed | Health Service Executive, National Public Health and Medical Officer Service, Provincial Institute for Hygiene, CNR Institute of Clinical Physiology and 18 more.
Type: | Journal: BMJ (Clinical research ed.) | Year: 2016

To provide contemporary estimates of the prevalence of microcephaly in Europe, determine if the diagnosis of microcephaly is consistent across Europe, and evaluate whether changes in prevalence would be detected using the current European surveillance performed by EUROCAT (the European Surveillance of Congenital Anomalies).Questionnaire and population based observational study.24 EUROCAT registries covering 570000 births annually in 15 countries.Cases of microcephaly not associated with a genetic condition among live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly at any gestation.Prevalence of microcephaly (1 Jan 2003-31 Dec 2012) analysed with random effects Poisson regression models to account for heterogeneity across registries.16 registries responded to the questionnaire, of which 44% (7/16) used the EUROCAT definition of microcephaly (a reduction in the size of the brain with a skull circumference more than 3 SD below the mean for sex, age, and ethnic origin), 19% (3/16) used a 2 SD cut off, 31% (5/16) were reliant on the criteria used by individual clinicians, and one changed criteria between 2003 and 2012. Prevalence of microcephaly in Europe was 1.53 (95% confidence interval 1.16 to 1.96) per 10000 births, with registries varying from 0.4 (0.2 to 0.7) to 4.3 (3.6 to 5.0) per 10000 ((2)=338, df=23, I(2)=93%). Registries with a 3 SD cut off reported a prevalence of 1.74 per 10000 (0.86 to 2.93) compared with those with the less stringent 2 SD cut off of 1.21 per 10000 (0.21 to 2.93). The prevalence of microcephaly would need to increase in one year by over 35% in Europe or by over 300% in a single registry to reach statistical significance (P<0.01).EUROCAT could detect increases in the prevalence of microcephaly from the Zika virus of a similar magnitude to those observed in Brazil. Because of the rarity of microcephaly and discrepant diagnostic criteria, however, the smaller increases expected in Europe would probably not be detected. Clear diagnostic criteria for microcephaly must be adopted across Europe.

Delvaux I.,Ghent University | Van Cauwenberghe J.,Ghent University | Den Hond E.,Flemish Institute for Technological Research | Schoeters G.,Flemish Institute for Technological Research | And 6 more authors.
Environmental Research | Year: 2014

The study aim was to investigate the association between prenatal exposure to endocrine disrupting chemicals (EDCs) and the body composition of 7 to 9 year old Flemish children. The subjects were 114 Flemish children (50% boys) that took part in the first Flemish Environment and Health Study (2002-2006). Cadmium, PCBs, dioxins, p,p'-DDE and HCB were analysed in cord blood/plasma. When the child reached 7-9 years, height, weight, waist circumference and skinfolds were measured. Significant associations between prenatal exposure to EDCs and indicators of body composition were only found in girls. After adjustment for confounders and covariates, a significant negative association was found in girls between prenatal cadmium exposure and weight, BMI and waist circumference (indicator of abdominal fat) and the sum of four skinfolds (indicator of subcutaneous fat). In contrast, a significant positive association (after adjustment for confounders/covariates) was found between prenatal p,p'-DDE exposure and waist circumference as well as waist/height ratio in girls (indicators of abdominal fat). No significant associations were found for prenatal PCBs, dioxins and HCB exposure after adjustment for confounders/covariates. This study suggests a positive association between prenatal p,p'-DDE exposure and indicators of abdominal fat and a negative association between prenatal cadmium exposure and indicators of both abdominal as well as subcutaneous fat in girls between 7 and 9 years old. © 2014 Elsevier Inc.

Van Larebeke N.,Free University of Brussels | Sioen I.,Ghent University | Hond E.D.,Flemish Institute for Technological Research | Nelen V.,Provincial Institute for Hygiene | And 5 more authors.
International journal of hygiene and environmental health | Year: 2015

In this paper, based on the Flemish biomonitoring programs, we describe the associations between internal exposure to organochlorine pollutants and to cadmium (measured in 2004-2005 for adults aged 50-65 years) and self-reported health status obtained through a questionnaire in November 2011. Dioxin-like activity in serum showed a significant positive association with risk of cancer for women. After adjustment for confounders and covariates, the odds ratio for an exposure equal to the 90th percentile was 2.4 times higher than for an exposure equal to the 10th percentile. For both men and women dioxin-like activity and serum hexachlorobenzene (HCB) showed a significant positive association with risk of diabetes and of hypertension. Detailed analysis suggested that an increase in BMI might be part of the mechanism through which HCB contributes to diabetes and hypertension. Serum dichlorodiphenyldichloroethylene (p,p'-DDE) concentration showed a significant positive association with diabetes and hypertension in men, but not in women. Serum polychlorinated biphenyl (PCB) 118 showed a significant positive association with diabetes in both men and women, and after adjustment for correlated exposures, also with hypertension in men. Urinary cadmium concentrations showed a significant positive association with hypertension. Urinary cadmium concentrations were (in 2004-2005) significantly higher in persons who felt in less than good health (in 2011) than in persons who felt in very good health. After adjustment for correlated exposures (to HCB, p,p'-DDE and PCB118) marker PCBs showed a significant negative association with diabetes and hypertension. Serum p,p'-DDE showed in men a significant negative association with risk of diseases based on atheromata. Our findings suggest that exposure to pollutants can lead to an important increase in the risk of diseases such as cancer, diabetes and hypertension. Some pollutants may possibly also decrease the risk of some health problems, although this requires confirmation by other approaches. Copyright © 2014 Elsevier GmbH. All rights reserved.

PubMed | Flemish Institute for Technological Research, Sint Dimphna Hospital, Provincial Institute for Hygiene, Hasselt University and 4 more.
Type: | Journal: Environmental research | Year: 2016

Traffic-related air pollution has been shown to induce neurotoxicity in rodents. Several recent epidemiological studies reported negative associations between residential outdoor air pollution and neurobehavioral performance. We investigated in a population of non-smoker adolescents the associations between the urinary concentration of trans, trans-muconic acid (t,t-MA-U), a metabolite of benzene and used as proxy-biomarker of traffic exposure, and two neurobehavioral domains, i.e. sustained attention and short-term memory.In the framework of an environmental health surveillance study in Flanders (Belgium), we examined between 2008 and 2014 grade nine high school students (n=895). We used reaction time, number of omission errors, and number of commission errors in the Continuous Performance Test to evaluate sustained attention, and for the evaluation of short-term memory we used maximum digit span forward and backward of the Digit Span Test. We measured blood lead (PbB) to assess the independent effect of t,t-MA-U on neurobehavioral outcomes.This neurobehavioral examination study showed that a ten-fold increase in t,t-MA-U was associated with a 0.14 SD lower sustained attention (95% Confidence Interval: -0.26 to -0.019; p=0.02) and a 0.17 SD diminished short-term memory (95% CI: -0.31 to -0.030; p=0.02). For the same increment in t,t-MA-U, the Continuous Performance Test showed a 12.2ms higher mean reaction time (95% CI: 4.86-19.5; p=0.001) and 0.51 more numbers of errors of omission (95% CI: 0.057-0.97; p=0.028), while no significant association was found with errors of commission. For the Digit Span Tests, the maximum digit span forward was associated with a 0.20 lower number of digits (95% CI: -0.38 to -0.026; p=0.025) and maximum digit span backward with -0.15 digits (95% CI: -0.32 to 0.022; p=0.088). These associations were independent of PbB, parental education and other important covariates including gender, age, passive smoking, ethnicity, urinary creatinine, time of the day, and examination day of the week. For PbB, an independent association was only found with mean reaction time of the Continuous Performance Test (19.1ms, 95% CI: 2.43-35.8; p=0.025).In adolescents, a ten-fold increase in the concentration of t,t-MA-U, used as a proxy-biomarker for traffic-related exposure, was associated with a significant deficit in sustained attention and short-term memory. The public health implications of this finding cannot be overlooked as the effect-size for these neurobehavioral domains was about 40% of the effect-size of parental education.

PubMed | Flemish Institute for Technological Research, Provincial Institute for Hygiene, Vrije Universiteit Brussel, Hasselt University and 2 more.
Type: Journal Article | Journal: Environmental science and pollution research international | Year: 2015

Within the Flemish Environment and Health studies (FLEHS I, 2002-2006, and FLEHS II, 2007-2012), pesticide exposure, hormone levels and degree of sexual maturation were measured in 14-15-year-old adolescents residing in Flanders (Belgium). In FLEHS II, geometric mean concentrations (with 95 % confidence interval (CI)) of 307 (277-341) and 36.5 ng L(-1) (34.0-39.2) were found for p,p-dichlorophenyldichloroethylene (p,p-DDE) and hexachlorobenzene (HCB). These values were respectively 26 and 60 % lower than levels in FLEHS I, 5 years earlier. Metabolites of organophosphorus pesticides (OPPs) and of para-dichlorobenzene were measured for the first time in FLEHS II, yielding concentrations of 11.4, 3.27 and 1.57 g L(-1) for the sum of dimethyl- and diethyl phosphate metabolites and 2,5-dichlorophenol (2,5-DCP), respectively. Data on internal exposure of HCB showed a positive correlation with sexual maturation, testosterone and the aromatase index for boys and with free thyroxine (fT4) and thyroid stimulating hormone (TSH) (both boys and girls). For both p,p-DDE and HCB, a negative association with sexual development in girls was found. The OPP metabolites were negatively associated with sex hormone levels in the blood of boys and with sexual maturation (both boys and girls). The pesticide metabolite 2,5-DCP was negatively correlated with free T4, while a positive association with TSH was reported (boys and girls). These results show that even exposure to relatively low concentrations of pesticides can have significant influences on hormone levels and the degree of sexual maturation in 14-15-year-old adolescents.

PubMed | Flemish Institute for Technological Research, Provincial Institute for Hygiene, Vrije Universiteit Brussel, Hasselt University and 2 more.
Type: Journal Article | Journal: International journal of environmental research and public health | Year: 2016

Prenatal chemical exposure has been frequently associated with reduced fetal growth by single pollutant regression models although inconsistent results have been obtained. Our study estimated the effects of exposure to single pollutants and mixtures on birth weight in 248 mother-child pairs. Arsenic, copper, lead, manganese and thallium were measured in cord blood, cadmium in maternal blood, methylmercury in maternal hair, and five organochlorines, two perfluorinated compounds and diethylhexyl phthalate metabolites in cord plasma. Daily exposure to particulate matter was modeled and averaged over the duration of gestation. In single pollutant models, arsenic was significantly associated with reduced birth weight. The effect estimate increased when including cadmium, and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) co-exposure. Combining exposures by principal component analysis generated an exposure factor loaded by cadmium and arsenic that was associated with reduced birth weight. MECPP induced gender specific effects. In girls, the effect estimate was doubled with co-exposure of thallium, PFOS, lead, cadmium, manganese, and mercury, while in boys, the mixture of MECPP with cadmium showed the strongest association with birth weight. In conclusion, birth weight was consistently inversely associated with exposure to pollutant mixtures. Chemicals not showing significant associations at single pollutant level contributed to stronger effects when analyzed as mixtures.

Vael C.,University of Antwerp | Verhulst S.L.,University of Antwerp | Nelen V.,Provincial Institute for Hygiene | Goossens H.,University of Antwerp | Desager K.N.,University of Antwerp
Gut Pathogens | Year: 2011

Background: Recent research on obesity has demonstrated that the intestinal microflora can have an important influence on host energy balance. The aim of the study was to investigate the relationship between the intestinal microflora and the body mass index in the first 3 years of life. Results: In a prospective study, a faecal sample from 138 infants was taken at the age of 3, 26 and 52 weeks and cultured on selective media for 6 bacterial genera. Between the age of 1 and 3 years the Body Mass Index Standard Deviation Score (BMI SDS) of these children was determined. The association between the intestinal flora and BMI SDS was assessed for each bacterial genus. A positive correlation was found between the Bacteroides fragilis concentration and the BMI SDS at the age of 3 and 26 weeks. The Staphylococcus concentration showed a negative correlation with the BMI SDS at the age of 3 and 52 weeks. A low intestinal ratio of Staphylococcus/Bacteroides fragilis at the age of 3 weeks, corresponding to a low Staphylococcus and a high Bacteroides fragilis concentration, was associated with a higher BMI SDS during the first three years of life. Conclusion: High intestinal Bacteroides fragilis and low Staphylococcus concentrations in infants between the age of 3 weeks and 1 year were associated with a higher risk of obesity later in life. This study could provide new targets for a better and more effective modulation of the intestinal microflora in infants. © 2011 Vael et al; licensee BioMed Central Ltd.

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